Journal of the National Comprehensive Cancer Network : JNCCN最新文献

{"title":"Adverse Family Outcomes in Children With B-Cell Acute Lymphoblastic Leukemia From the Multicenter Trial Children's Oncology Group AALL0932.","authors":"Rozalyn L Rodwin, John A Kairalla, Emily Hibbitts, Lyn M Balsamo, Meenakshi Devidas, Brenna Mossman, Alexandra Dreyzin, Naomi J Winick, Lillian Sung, Claire Conley, William L Carroll, Stephen P Hunger, Elizabeth Raetz, Kirsten K Ness, Mignon L Loh, Reuven J Schore, Anne L Angiolillo, Nina S Kadan-Lottick","doi":"10.6004/jnccn.2026.7048","DOIUrl":"10.6004/jnccn.2026.7048","url":null,"abstract":"<p><strong>Background: </strong>Treatment for B-cell acute lymphoblastic leukemia (B-ALL) lasts >2 years and can impact families. The Children's Oncology Group multicenter therapeutic trial AALL0932 randomized patients with NCI standard-risk, average-risk B-ALL (NCI-SR AR B-ALL) to receive maintenance vincristine/dexamethasone every 4 or 12 weeks (VCR/DEX4 or VCR/DEX12, respectively). Embedded in AALL0932, this study aimed to (1) longitudinally measure adverse family outcomes overall, and (2) determine whether patients on the VCR/DEX4 regimen (vs VCR/DEX12) had fewer adverse family outcomes.</p><p><strong>Methods: </strong>Patients with NCI-SR AR B-ALL who were offered enrollment on the multicenter randomized-controlled therapeutic trial AALL0932 were aged ≥4 years with an English-speaking parent. Parent-reported surveys were administered at T1-T5 (approximately 2, 9, 18, 26, and 38 months after diagnosis, respectively; T5 was assessed only in boys) and assessed household changes since leukemia diagnosis, leukemia-related household expenses in the past 4 weeks, unhealthy family functioning (Family Assessment Device score >2), and parents' perceived child vulnerability (Child Vulnerability Scale ≥10). Postrandomization outcomes at T3 and T4 were compared between treatment groups using generalized linear mixed models and multivariable logistic regression models, as appropriate, adjusting for race and ethnicity.</p><p><strong>Results: </strong>Among 555 participants with completed evaluations, 420 were randomized (mean [SD] age, 6.0 [1.6] years; 45.7% female). At T1, 56.2% of randomized participants reported household changes since diagnosis (81.2% by T4), 88.6% reported ≥$100 in leukemia-related household expenses in the past 4 weeks (61.5% at T4), 19.0% had unhealthy family functioning (23.9% at T4), and 55.8% perceived their child as vulnerable (62.5% at T4). In multivariable models, VCR/DEX4 (vs VCR/DEX12) had an increased likelihood of reporting ≥$100 in leukemia-related expenses in the past 4 weeks (odds ratio, 1.73; 95% CI, 1.03-2.91), but other outcomes were similar between treatment arms.</p><p><strong>Conclusions: </strong>B-ALL family burdens develop early. Reducing maintenance VCR/DEX frequency may decrease expenses but not other outcomes. Interventions are needed to support families early and throughout ALL therapy.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":"24 10","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Re: Excision With Total Margin Control Versus Vertical Section Margin Assessment for NCCN Very High-Risk Cutaneous Squamous Cell Carcinoma.","authors":"Joseph Skitzki, Mark DeLacure, Anthony Tufaro","doi":"10.6004/jnccn.2026.7077","DOIUrl":"10.6004/jnccn.2026.7077","url":null,"abstract":"","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection Patterns of Breast Cancer Recurrence and Contralateral New Primaries in a Large Integrated Health System.","authors":"Ali M Duffens, Cecile A Laurent, Isaac J Ergas, Janise M Roh, Vignesh A Arasu, Lawrence H Kushi, Raymond Liu","doi":"10.6004/jnccn.2026.7044","DOIUrl":"https://doi.org/10.6004/jnccn.2026.7044","url":null,"abstract":"<p><strong>Background: </strong>Optimizing surveillance for the growing population of breast cancer survivors remains a challenge. Although screening guidelines for initial breast cancer are well established, current surveillance guidelines recommending routine provider examinations rely heavily on expert consensus rather than real-world data. Limited evidence exists on how second breast cancer events, including recurrences and contralateral new primary breast cancer, are actually detected in practice.</p><p><strong>Methods: </strong>We analyzed data from the Pathways Study, a prospective cohort of women diagnosed with stage I-III breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through 2021. We assessed the timing, outcomes, and detection modality of second events, categorized as patient-reported symptoms, surveillance mammogram, provider examination, incidental finding, or ancillary testing.</p><p><strong>Results: </strong>Of 4,417 eligible women, 792 (17.9%) experienced a second event: 577 (13.1%) had a recurrence and 215 (4.9%) developed a contralateral new primary. Most recurrences were metastatic (70.0%) and symptom-detected (78.0%), with only 9.9% found via surveillance mammogram and 5.0% by provider examination. In contrast, 82.8% of contralateral new primaries were detected via mammogram, with only 0.5% found on provider examination. Recurrences clustered within 5 years postdiagnosis and were associated with poor survival, whereas contralateral primaries occurred steadily over time with more favorable outcomes.</p><p><strong>Conclusions: </strong>In this large, diverse cohort with high access to survivorship care, routine provider examinations rarely detected second breast cancer events. Detection patterns differed by event type, with recurrences typically early, metastatic, and symptom-detected, whereas contralateral new primaries were found via imaging across the follow-up period. These findings support consideration of more individualized, risk-adapted surveillance strategies that emphasize symptom awareness, patient education, and appropriate use of imaging, rather than uniform examination-based approaches. Further research is needed to evaluate emerging tools, such as circulating tumor DNA and artificial intelligence, to improve the timely detection of second events and survivorship outcomes.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":"1-8"},"PeriodicalIF":16.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy for Pleural Mesothelioma.","authors":"Logan N Roof, James P Stevenson","doi":"10.6004/jnccn.2026.7070","DOIUrl":"10.6004/jnccn.2026.7070","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of pleural mesothelioma (PM) over the past decade. This review summarizes the history of immunotherapy in PM, covering studies of single-agent immunotherapy, combination checkpoint blockade, the integration of ICIs into frontline therapeutic strategies, and ICI-VEGF combinations. Also discussed are the emerging role of biomarkers in guiding first-line therapy selection for patients with PM and novel therapeutic approaches. Dual checkpoint blockade targeting PD-1 and CTLA-4 demonstrated clinical efficacy in early-phase studies and led to the pivotal phase III CheckMate 743 trial, which established nivolumab and ipilimumab as a standard first-line systemic therapy for PM, particularly in patients with nonepithelioid histology. Since that time, other combination therapy approaches have been explored. For example, chemoimmunotherapy studies have evaluated ICIs, including pembrolizumab and durvalumab, in combination with platinum chemotherapy, with pembrolizumab plus platinum-doublet chemotherapy expanding the approved frontline treatment options for PM. VEGF inhibition, validated in the phase III MAPS study, provided a biologic rationale for combining antiangiogenic agents with ICIs. This prompted investigation of bevacizumab in combination with atezolizumab and chemotherapy in the BEAT-meso study. Unfortunately, this combination did not provide meaningful benefit in this setting. Optimal patient selection and treatment sequencing remain undefined. Although robust data support the use of second-line immunotherapy after first-line chemotherapy, there is a paucity of evidence regarding the efficacy of chemotherapy following frontline ICI. Despite advancements in therapeutic options in PM, biomarker-driven treatment selection remains limited at this time. Future large clinical studies must incorporate validated and standardized biomarker subanalyses, including approaches such as circulating tumor DNA and multiomics, for biomarkers to become clinically relevant in this heterogeneous malignancy. Finally, novel therapeutic strategies, including bispecific antibodies, targeted therapies, perioperative immunotherapy, vaccines, and cellular therapies, are under active investigation and may further expand treatment options for patients with PM.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors for Pneumonitis Induced by Combined Radiotherapy and Immunotherapy: A Multicenter Prospective Study.","authors":"Lingyan Xiao, Qian Li, Ying Li, Dewen Wang, Sheng Wang, Zhijie Fan, Duo Xu, Yulong Yu, Guang Han, Xianglin Yuan, Bo Liu","doi":"10.6004/jnccn.2026.7039","DOIUrl":"10.6004/jnccn.2026.7039","url":null,"abstract":"<p><strong>Background: </strong>The combination of radiotherapy (RT) and immune checkpoint inhibitors (ICIs) has become an important therapeutic approach for lung cancer. However, pneumonitis remains a major treatment-related toxicity of this therapeutic approach, and the risk factors for pneumonitis associated with combined RT and ICIs under different treatment sequences have not been clearly defined.</p><p><strong>Patients and methods: </strong>Patients with lung cancer who received thoracic RT were prospectively enrolled from 3 centers. Pneumonitis was assessed according to CTCAE version 4.0 by a multidisciplinary team. Cox proportional hazards models were used to identify factors associated with pneumonitis.</p><p><strong>Results: </strong>During a median follow-up of 28.2 months, 133 of 380 (35.0%) patients developed symptomatic pneumonitis (grade ≥2). Treatment with ICIs was associated with an increased risk of symptomatic pneumonitis (hazard ratio [HR], 1.69; 95% CI, 1.20-2.39; P=.003). Among 170 patients treated with ICIs, 89 received ICIs before RT (ICI-first group) and 81 received ICIs after RT (RT-first group). In the ICI-first group, 42 (47.2%) patients developed symptomatic pneumonitis, and an interval of <21 days between ICI administration and RT and a higher percentage of lung volume receiving ≥20 Gy (V20) were associated with an increased risk of pneumonitis. In the RT-first group, 32 (39.5%) patients developed symptomatic pneumonitis, with older age and higher V20 identified as risk factors.</p><p><strong>Conclusions: </strong>Administration of ICIs before RT significantly increases the risk of pneumonitis in patients receiving thoracic RT. The dosimetric factor V20 consistently emerged as a key determinant of pneumonitis risk in both the ICI-first and RT-first groups. These findings aid in preventing the occurrence of pneumonitis induced by combined RT and ICIs, thereby improving patients' quality of life and survival outcomes.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triplet Immunosuppression for Immune Checkpoint Inhibitor-Related Adverse Events is Associated With High Infection Risk.","authors":"Ross D Merkin, Tristan L Lim, Daniel Restifo, Sherin J Rouhani, Lorena Pantano, Matthew M Lei, Leyre Zubiri, Yevgeniy R Semenov, Maysa Vilbert, Bryan L Peacker, Steven M Blum, Michael J Dennis, Elizabeth I Buchbinder, Sarah P Hammond, Kerry L Reynolds","doi":"10.6004/jnccn.2026.7068","DOIUrl":"https://doi.org/10.6004/jnccn.2026.7068","url":null,"abstract":"<p><strong>Background: </strong>The use of multiagent immunosuppressive therapy (IST) to treat immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) increases the risk of infection. Time-normalized infection rates in a large cohort have not been previously reported. Predictors of opportunistic and nonopportunistic infections (OIs and non-OIs, respectively) and infection severity are poorly understood.</p><p><strong>Methods: </strong>We conducted a retrospective chart review of patients treated with ICIs and identified those who received simultaneous multiagent IST for irAE treatment, defined as at least 1 supraphysiologic-dose corticosteroid (steroid) and 2 steroid-sparing ISTs administered within 90 days of one another. Patients who received ≤2 ISTs were not included in the analysis. Total exposure duration and the number of OIs and non-OIs occurring during ICI alone, 1 IST, 2 ISTs, and ≥3 ISTs were used to calculate infection rates per 1,000 exposure-days. Significance was assessed using the Poisson test. The cumulative incidence function and Fine-Gray test were applied to identify clinical features associated with infection risk.</p><p><strong>Results: </strong>Between June 2011 and February 2024, 20,930 patients received ICI therapy. A total of 142 (0.68%) patients received 3 ISTs and were included in the analysis. Among the 142 patients, 74 experienced a total of 152 infections, including 132 non-OIs in 68 patients and 20 OIs in 17 patients. Cytomegalovirus reactivation accounted for 10 of 20 OIs. Per 1,000 patient-days, the OI density was 0 during ICI alone, 0.06 with 1 IST, 0.57 with 2 ISTs, and 0.42 with ≥3 ISTs (P<.0001). The corresponding non-OI densities were 0.85, 0.90, 2.04, and 4.14, respectively (P<.0001). When mild and moderate infections were omitted, the same trend was observed. In subgroup analyses, age >65 years was a predictor of OIs (P=.046) but not non-OIs, whereas cardiac irAEs were a predictor of non-OIs (P=.018) but not OIs.</p><p><strong>Conclusions: </strong>These data support the development of improved strategies for infection screening, prophylaxis, and monitoring in patients receiving multiagent IST for irAE treatment.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":"1-8"},"PeriodicalIF":16.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coping Strategies Among Early-Phase Cancer Clinical Trial Participants.","authors":"Anh B Lam, Andrea Pelletier, Cynthia Moore, Sienna Durbin, Kaitlyn Lynch, Laura Petrillo, Rachel Jimenez, Mary Boulanger, Leah Thompson, Viola Bame, Vaishnavi Yalala, Nicholas Ollila, Benjamin Malowitz, Casandra McIntyre, Dejan Juric, Ryan David Nipp, Debra Lundquist","doi":"10.6004/jnccn.2026.7037","DOIUrl":"10.6004/jnccn.2026.7037","url":null,"abstract":"<p><strong>Background: </strong>Individuals with cancer often use numerous coping strategies. However, little is known about coping behavior among patients enrolled on early-phase cancer clinical trials (EPCTs).</p><p><strong>Methods: </strong>We prospectively enrolled adults with cancer initiating EPCTs at Massachusetts General Hospital from April 2021 to March 2025. Participants completed surveys at the time of EPCT enrollment assessing coping (Brief COPE [Coping Orientation to Problems Experienced]; scores range 0-6), quality of life (QoL; Functional Assessment of Cancer Therapy-General [FACT-G]), depression and anxiety symptoms (Patient Health Questionnaire-4 [PHQ-4]), symptom burden (Edmonton Symptom Assessment Scale [ESAS]), and financial well-being (Comprehensive Score for Financial Toxicity [COST]). We used regression models to explore associations of coping strategies with patient-reported and clinical outcomes.</p><p><strong>Results: </strong>Among 195 participants enrolled, 188 completed the survey assessments (96.4% response rate). Among these participants (median age, 63.5 [range, 31.8-88.6]; 56.4% female), the most common cancer types were gastrointestinal (34.0%) and breast (20.7%). At the time of EPCT enrollment, patients' coping strategies included acceptance (mean Brief COPE score, 4.77), emotional support (mean score, 4.60), active coping (mean score, 4.25), positive reframing (mean score, 3.11), religion (mean score, 2.85), self-blame (mean score, 0.88), denial (mean score, 0.62), and behavioral disengagement (mean score, 0.35). Greater use of approach-oriented strategies (acceptance, emotional support, and positive reframing) and lower use of avoidant strategies (denial, self-blame, and behavioral disengagement) were associated with better QoL, fewer symptoms of depression and anxiety, lower symptom burden, and greater financial well-being (P<.05). Greater use of denial coping was associated with a lower risk of hospitalizations (hazard ratio [HR], 0.76; P=.007). Use of acceptance coping was associated with lower odds of completing the dose-limiting toxicity (DLT) period (odds ratio, 0.57; P=.023) and with a shorter time on trial (HR, 1.16; P=.011). Use of emotional support coping was associated with a shorter time on trial (HR, 1.13; P=.016) and worse survival (HR, 1.17; P=.005). Use of religion (HR, 1.09; P=.035) and positive reframing (HR, 1.11; P=.039) coping strategies was associated with worse survival.</p><p><strong>Conclusions: </strong>In this cohort of EPCT participants, we found associations of coping behaviors with patient outcomes. Specifically, approach-oriented coping strategies correlated with higher QoL and lower distress. Interventions seeking to enhance outcomes in this population should target the diverse coping strategies used by EPCT participants.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Study on the Influence of Physical Activity in Managing Fatigue in Patients With Colorectal Cancer.","authors":"Louisa Liu, Elham Kazemian, Nicole C Loroña, Celina Shirazipour, Jun Gong, Sylvia L Crowder, Nathalie Nguyen, Victoria Damerell, Kathi Mooney, Mary C Playdon, Cornelia M Ulrich, Christopher I Li, David Shibata, Adetunji T Toriola, Jennifer Ose, Anita R Peoples, Sheetal Hardikar, Erin M Siegel, Julienne E Bower, Biljana Gigic, Aasha I Hoogland, Xiaoyin Li, Brent J Small, Howard Kaufman, Heather S L Jim, Jane C Figueiredo","doi":"10.6004/jnccn.2026.7035","DOIUrl":"10.6004/jnccn.2026.7035","url":null,"abstract":"<p><strong>Background: </strong>Fatigue is a prevalent and debilitating symptom among patients with cancer. Physical activity (PA) may help reduce fatigue and improve quality of life (QoL). This study evaluated longitudinal associations between PA, fatigue, and QoL across the cancer care continuum.</p><p><strong>Methods: </strong>Data were analyzed from 1,718 participants in a prospective multicenter cohort. Self-reported PA was assessed at baseline and up to 24 months post-diagnosis using a questionnaire based on the International PA Questionnaire (IPAQ). Metabolic equivalent task (MET)-minutes per week were calculated for walking, moderate, vigorous, and total physical activity. Fatigue and QoL were measured using the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30). Mixed-effects models evaluated associations between PA and outcomes. Lagged fluctuation models examined temporal relationships, separating between-person and within-person effects.</p><p><strong>Results: </strong>PA levels increased steadily from diagnosis through 24 months, coinciding with reduced fatigue and improved QoL. Higher PA was consistently linked to better fatigue and QoL outcomes. Walking was associated with lower odds of severe fatigue at 6 months (odds ratio [OR], 0.78; 95% CI, 0.62-0.98; P=.031) and 12 months (OR, 0.74; 95% CI, 0.59-0.94; P=.014), with higher odds of better QoL at all follow-up points. Vigorous activity showed the strongest protective effect against fatigue at 24 months (OR, 0.65; 95% CI, 0.45-0.94; P=.023). In patients with nonmetastatic disease, protective associations were observed across all activity types and time points. Lagged models indicated that higher average vigorous activity predicted lower future fatigue (P<.001).</p><p><strong>Conclusions: </strong>Greater PA, particularly walking, was associated with lower fatigue and improved QoL, especially in patients with early-stage disease. The posttreatment period (approximately 1 year post-diagnosis) may represent an important window for behavioral intervention. Findings support stage- and recovery phase-specific guidance and highlight walking as a scalable, low-risk target for survivorship care.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting KRAS-Mutant Lung Cancers.","authors":"Edoardo Garbo, Pietro Scaparone, Hui Jing Hoe, Jia Luo, Alice T Shaw, Chiara Ambrogio, Biagio Ricciuti","doi":"10.6004/jnccn.2026.7038","DOIUrl":"10.6004/jnccn.2026.7038","url":null,"abstract":"<p><p>KRAS mutations are the most common oncogenic driver alterations in non-small cell lung cancer (NSCLC) and define biologically heterogeneous diseases shaped by mutation subtype, co-mutation patterns, and immune contexture. Recent advances in structural and chemical biology have transformed KRAS from an undruggable target into a rapidly expanding therapeutic vulnerability. The first allele-specific inhibitors, sotorasib and adagrasib, validated KRASG12C as a druggable dependency, changing the treatment paradigm for previously treated KRASG12C NSCLC, although primary, acquired, and adaptive resistance remain widespread. Next-generation inhibitors such as divarasib improve potency and tolerability but continue to face resistance through secondary KRAS alterations, bypass receptor tyrosine kinase (RTK) signaling, and adaptive MAPK reactivation. These challenges have spurred the development of KRAS(ON) inhibitors, dual ON/OFF inhibitors, and broader pan-KRAS and pan-RAS agents capable of targeting multiple oncogenic variants, including G12D, G12V, G12X, G13X, and Q61X. Early clinical results with tricomplex RAS(ON) inhibitors (eg, daraxonrasib) and G12D-selective agents (eg, zoldonrasib) demonstrate promising activity in subsets historically lacking targeted options. In parallel, rational combination strategies aimed at enhancing overall efficacy, such as RTK, SHP2/SOS1, or PD-1/PD-L1 blockade, together with emerging modalities including RAF-MEK clamps, adoptive cell therapies, and KRAS vaccines, are broadening the therapeutic landscape. This review comprehensively summarizes KRAS biology, therapeutic advances, mechanisms of resistance, and emerging strategies that are reshaping the treatment landscape of KRAS-mutant NSCLC.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spillover Effects of Medicaid Expansion on Insurance Coverage, Diagnosis, and Survival Among Low-Income Older Patients With Cancer.","authors":"Kewei Sylvia Shi, Xu Ji, K Robin Yabroff, Justin M Barnes, Fumiko Chino, Xuesong Han","doi":"10.6004/jnccn.2026.7040","DOIUrl":"10.6004/jnccn.2026.7040","url":null,"abstract":"<p><strong>Background: </strong>Medicaid expansion under the Affordable Care Act primarily benefits adults aged <65 years but may also indirectly benefit individuals aged ≥65 years. This study examines the associations of Medicaid expansion with insurance coverage and cancer outcomes among older patients residing in low-income areas.</p><p><strong>Patients and methods: </strong>Using the National Cancer Database, we identified patients aged ≥65 years, newly diagnosed with cancer 2010-2021, and residing in areas with median household income <200% of the federal poverty level. Using the quasi-experimental difference-in-differences design, multivariable models compared dual Medicare-Medicaid enrollment or Medicaid-only coverage, stage at diagnosis, treatment initiation, and 2-year overall survival before and after Medicaid expansion in expansion versus non-expansion states.</p><p><strong>Results: </strong>Our sample included 1,461,540 patients. Dual Medicare-Medicaid or Medicaid-only coverage increased in Medicaid expansion states (10.3%-11.3%) and decreased in Medicaid non-expansion states (9.4%-8.1%), resulting in a net increase of 1.25 percentage points (ppt; 95% CI, 1.02-1.48). Early-stage cancer diagnoses decreased overall, driven by prostate cancer, but declined less in expansion states than in non-expansion states, with a net adjusted relative increase of 1.00 ppt (95% CI, 0.59-1.41). Such protective effects were stronger for lung/bronchus and head and neck cancers. Treatment initiation within 30 days also decreased less in expansion states than non-expansion states, with a net adjusted increase of 0.74 ppt (95% CI, 0.34-1.14). Two-year overall survival increased more in expansion states (58.8%-62.4%) than non-expansion states (59.2%-62.5%), leading to a net increase of 0.70 ppt (95% CI, 0.35-1.04). Such increase was most notable for stage IV, lung/bronchus, kidney, and bladder cancers.</p><p><strong>Conclusions: </strong>Medicaid expansion was associated with increased Medicaid coverage, attenuated declines in early-stage diagnosis and timely treatment initiation, and improved survival among low-income older patients with cancer, highlighting important spillover benefits beyond the target population.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}